Selenium Supplementation May Adversely Affect Prostate Cancer Risk

by | Feb 1, 2021 | 2018, Cancer, Diabetes, Men's Health - Prostate, Selenium

Written by Angeline A. De Leon, Staff Writer. This Mendelian randomization analysis does not support the use of selenium supplementation in prostate cancer prevention and suggests that supplementation might increase the risk of advanced prostate cancer and type 2 diabetes.

prostate cancerAccording to estimates from the American Cancer Society, prostate cancer represents the most commonly diagnosed form of non-skin cancer and the second leading cause of cancer-related mortality among US men over the past decade 1. The effective prevention of prostate cancer has warranted experimentation with nutraceutical supplements such as selenium, which possesses strong antioxidant properties and demonstrates potential anti-carcinogenic effects 2. Randomized controlled trials have found evidence suggesting that selenium, in combination with vitamin E and beta-carotene, can significantly reduce the risk of prostate cancer, as well as overall cancer mortality 3,4. However, some of the largest clinical studies on selenium and prostate cancer have reported contradictory findings, suggesting that selenium supplementation has no preventative effect in men at high-risk for prostate cancer 5 and may even increase risk of carcinogenic and adverse metabolic effects (type 2 diabetes) (The Selenium and Vitamin E Cancer Prevention Trial, SELECT study) 6. In a 2018 study published in the Journal of the National Cancer Institute, researchers conducted a Mendelian randomization analysis (MR, research method using measured genetic variants to determine causal effect on disease outcome)7 to examine the effects of selenium-raising alleles on prostate cancer risk and to compare findings to those obtained in the SELECT study.

A two-sample MR study 8 was carried out using the summary genome-wide association study (GWAS) statistics of 72,720 men (44,825 case subjects, 27,904 controls) who previously participated in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) Consortium. A genetic instrument was created to proxy selenium based on 11 single nucleotide polymorphisms (SNPs) that were found to be robustly associated with circulating selenium concentrations in GWAS data. Odds Ratios (ORs) for overall prostate cancer, advanced prostate cancer, as well as type 2 diabetes (analyzed using summary GWAS statistics from a meta-analysis of 49,266 diabetic subjects and 249,906 controls), were calculated per 114 µg/L increase in circulating selenium.

MR analyses revealed that a 114 µg/L increase in blood selenium was not associated with overall prostate cancer risk (OR = 1.01, 95% Confidence Interval: 0.89 to 1.13, p = 0.93). However, elevated selenium was found to be weakly associated with both advanced prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49, p = 0.07) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43, p = 0.11), in line with data from the SELECT study (advanced prostate cancer OR = 1.21, 95% CI = 0.97 to 1.52; type 2 diabetes OR = 1.07, 95% CI = 0.87 to 1.18) (6).

In contrast to some of the findings reported by previous studies 3,4 results from the present trial do not support a preventative role of selenium supplementation in prostate cancer. Rather, data corroborate findings from the SELECT study, indicating that a 114 µg/L increase in circulating selenium may actually increase risk of advanced prostate cancer and type 2 diabetes. Overall, the therapeutic use of selenium to prevent prostate cancer appears to be inadvisable, and the adverse effects of selenium supplementation deserve further investigation. Strengths of the current trial relate to its high statistical power and precision due to the use of data from large GWAS meta-analyses. A notable weakness pertains to the study’s inability to verify the effects of selenium in high-grade prostate cancer, only advanced prostate cancer (due to insufficient data). In addition, the association of selenium SNPs with betaine, a potential risk factor for type 2 diabetes 9, is a limitation, as it would theoretically violate the assumptions of MR analysis. For the future, MR analyses confirming the effects of selenium in relation to vitamin E and beta-carotene for prostate cancer risk would also be useful.

Source: Yarmolinsky J, Bonilla C, Haycock PC, et al. Circulating selenium and prostate cancer risk: a Mendelian randomization analysis. J Natl Cancer Inst. 2018; 110(9): djy081. DOI: 10.1093/jnci/djy081.

© The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)

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Posted February 1, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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